title: A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci.
abstract: Allergic disease is very common and carries substantial public-health burdens. We conducted a meta-analysis of genome-wide associations with self-reported cat, dust-mite and pollen allergies in 53,862 individuals. We used generalized estimating equations to model shared and allergy-specific genetic effects. We identified 16 shared susceptibility loci with association P<5×10(-8), including 8 loci previously associated with asthma, as well as 4p14 near TLR1, TLR6 and TLR10 (rs2101521, P=5.3×10(-21)); 6p21.33 near HLA-C and MICA (rs9266772, P=3.2×10(-12)); 5p13.1 near PTGER4 (rs7720838, P=8.2×10(-11)); 2q33.1 in PLCL1 (rs10497813, P=6.1×10(-10)), 3q28 in LPP (rs9860547, P=1.2×10(-9)); 20q13.2 in NFATC2 (rs6021270, P=6.9×10(-9)), 4q27 in ADAD1 (rs17388568, P=3.9×10(-8)); and 14q21.1 near FOXA1 and TTC6 (rs1998359, P=4.8×10(-8)). We identified one locus with substantial evidence of differences in effects across allergies at 6p21.32 in the class II human leukocyte antigen (HLA) region (rs17533090, P=1.7×10(-12)), which was strongly associated with cat allergy. Our study sheds new light on the shared etiology of immune and autoimmune disease.
authors.affiliation: 23andMe, Inc., Mountain View, California, USA. dhinds@23andMe.com
authors.forename: David A
authors.initials: DA
authors.lastname: Hinds
authors.forename: George
authors.initials: G
authors.lastname: McMahon
authors.forename: Amy K
authors.initials: AK
authors.lastname: Kiefer
authors.forename: Chuong B
authors.initials: CB
authors.lastname: Do
authors.forename: Nicholas
authors.initials: N
authors.lastname: Eriksson
authors.forename: David M
authors.initials: DM
authors.lastname: Evans
authors.forename: Beate
authors.initials: B
authors.lastname: St Pourcain
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ring
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Mountain
authors.forename: Uta
authors.initials: U
authors.lastname: Francke
authors.forename: George
authors.initials: G
authors.lastname: Davey-Smith
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Timpson
authors.forename: Joyce Y
authors.initials: JY
authors.lastname: Tung
mesh_terms: D000328:Adult; D000368:Aged; D000485:Allergens / Q000276:immunology; D000818:Animals; D002415:Cats; D015331:Cohort Studies; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D039981:Pyroglyphidae / Q000276:immunology; D057566:Self Report; D055815:Young Adult
chemical_list: D000485:Allergens